Epilepsia
-
Review Meta Analysis
The adverse event profile of pregabalin: a systematic review and meta-analysis of randomized controlled trials.
Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available randomized controlled trials (RCTs) of a given AED to fully uncover its tolerability profile. We aimed at identifying treatment emergent adverse events (AEs) associated with pregabalin through a systematic review and meta-analysis of all available RCTs. We also assessed the association between serious AEs and pregabalin, and investigated whether pregabalin AEs display a dose-response relationship. ⋯ Individuals starting treatment with pregabalin are at increased risk for several AEs, particularly those affecting cognition/coordination. Pregabalin AEs appear according to a selective dose-response pattern, possibly reflecting the severity of dysfunction of distinct anatomic structures. These findings may aid clinicians in providing better patient management, and support the value of including in meta-analyses of AED tolerability profiles RCTs performed in different conditions.
-
Multicenter Study Clinical Trial
Phenobarbital for neonatal seizures in hypoxic ischemic encephalopathy: a pharmacokinetic study during whole body hypothermia.
Therapeutic hypothermia has recently been introduced to treat term newborns with hypoxic-ischemic encephalopathy, of whom more than half have seizures. Phenobarbital is widely used to treat neonatal seizures, but it is unknown whether its pharmacokinetics is affected by hypothermia. We evaluated the influence of hypothermia on phenobarbital pharmacokinetics in asphyxiated newborns. ⋯ Phenobarbital administered to newborns under whole body hypothermia results in higher plasma concentrations and longer half-lives than expected in normothermic newborns.
-
Editorial Review
Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma.
Despite the development of various new antiepileptic drugs (AEDs) since the early 1990s, the available evidence indicates that the efficacy and tolerability of drug treatment of epilepsy has not substantially improved. What are the reasons for this apparent failure of modern AED development to discover drugs with higher efficacy? One reason is certainly the fact that, with few exceptions, all AEDs have been discovered by the same conventional animal models, particularly the maximal electroshock seizure test (MES) in rodents, which served as a critical gatekeeper. These tests have led to useful new AEDs, but obviously did not help developing AEDs with higher efficacy in as yet AED-resistant patients. ⋯ The failure of AED development has led to increasing disappointment among clinicians, basic scientists, and industry and may halt any further improvement in the treatment of epilepsy unless we find ways out of this dilemma. Therefore, we need new concepts and fresh thinking about how to radically change and improve AED discovery and development. In this respect, the authors of this critical review will discuss several new ideas that may hopefully lead to more efficacious drug treatment of epilepsy in the future.
-
Randomized Controlled Trial Multicenter Study
A multicenter, randomized, placebo-controlled trial of levetiracetam in children and adolescents with newly diagnosed absence epilepsy.
To evaluate the potential efficacy of levetiracetam as an antiabsence agent in children and adolescents with newly diagnosed childhood or juvenile absence epilepsy. ⋯ Although superiority to placebo just failed to reach statistical significance for the primary end point, the overall findings are consistent with levetiracetam having modest efficacy against absence seizures. Further controlled trials exploring larger doses and an active comparator are required to determine the role of levetiracetam in the treatment of absence epilepsy.
-
Randomized Controlled Trial Comparative Study
Intranasal versus intravenous lorazepam for control of acute seizures in children: a randomized open-label study.
Intravenous lorazepam is considered the drug of first choice for control of acute convulsive seizures. However, resource or personnel constraints necessitate the study of alternative routes and medications. This study compared the efficacy and adverse effects of intranasal versus intravenous lorazepam in children aged 6-14 years who presented with acute seizures. ⋯ Intranasal administration of lorazepam is not found to be inferior to intravenous administration for termination of acute convulsive seizures in children.